Exposure to radioactive radiation of various levels and types is becoming increasingly common. For example, whole body irradiation is utilized to induce immunosuppression in patients with leukemia or autoimmune disease. Various malignancies such as those in the head-neck region are often treated by radiotherapy.
In addition, individuals are occasionally exposed to radiation from their environment. During the past 50 years four major industrial radioactive accidents were reported in Kistym (USSR) and Wind-Scale (England) in 1957, Three Mile Island (USA) in 1979 and in Chernobyl (USSR) in 1986. These accidents (and especially the last) resulted in widespread exposure to various levels of radioactivity.
It is well known that irradiation often leads to functional alterations in organs and subsequent development of various disorders and diseases, especially malignant diseases. For example, irradiation of the head and neck regions causes significant damage to structures and functions in the oral cavity.sup.(1). Leukemia, thyroid, breast, lung and gastrointestinal cancers are the most frequent radiation induced diseases. The role of free radicals in carcinogenesis, radiation induced damages and immunodeficiency is well known. The reactive oxygen species, superoxide hydrogen peroxide and hydroxyl free radicals are generated in vitro as normal metabolites. Oxidative DNA damage is a major cause of endogenous mutations. The fraction of reversible and repairable radiation-induced damages may be increased by administrating radioprotective and cancer preventing agents such as antioxidants.
Beta-carotene (the precursor of vitamin A) is one of the most effective substances known to quench the activity of exited and singlet oxygen, and has been reported to be a potent free radical quencher, singlet oxygen scavenger and lipid antioxidant.sup.(2). Supplemental vitamin A as well as .beta.-carotene diminish the toxicity due to local X-ray or whole body irradiation.sup.(3). Both of them also inhibit carcinogenesis caused by some chemicals or UV irradiation. In animal models as well as human pre malignant diseases of the oral cavity, .beta.-carotene is able to reduce the incidence of malignant diseases of the oral cavity, to reduce the incidence of malignant transformation and to cure the leukoplakia or papillomas.
In contrast to other retinoids, .beta.-carotene does not influence the plasma lipid level and is not toxic, qualities which makes it an excellent candidate for chemoprevention of cancer.
Two strains of Dunaliella, a unicellular, biflagellate, wall-less green alga, are capable of producing very large amounts of .beta.-carotene, Dunaliella salina Teod. and Dunaliella bardawil.sup.(4). D. bardawil is a halotolerant alga whose .beta.-carotene content comprises about 50% all-trans-.beta.-carotene with the remainder composed mostly of 9-cis-.beta.-carotene and a few other .beta.-carotene isomers.sup.(5). A process has been described for cultivating D. bardawil so as to obtain algae containing up to about 5% by weight of .beta.-carotene.sup.(6). Later developments of the process increased the percentage to more than 8%.sup.(4,9). It has been shown that the natural isomer mixture of .beta.-carotene which is accumulated in the alga Dunaliella bardawil is accumulated in fatty tissues of rats and chicks to an extent which is about 10 fold higher than that observed by feeding the synthetic all-trans .beta.-carotene.sup.(7).
WO 93/24454 describes a carotenoid composition derived from Dunaliella algae in which the .beta.-carotene content is predominantly 9-cis .beta.-carotene. There is no mention of any medical applications.
Various carotenoid-enriched Dunaliella commercial products are available such as Betatene.TM. (produced by the Henkel Corp., Germany) and Nutrilite.TM. (Amway, Inc., U.S.A.). These products are oil extracts of carotenoids from Dunaliella.